The purpose of this investigation is to further elucidate the structure and genetic control of the synthesis of IgA. There are two subclasses of rabbit IgA, IgA-f and IgA-g, each with its own set of allotypic specificities. One of our goals is to correlate the structure of the alpha chains with the allotypic specificities. There are several cross-reactions between the various allotypic specificities and by a combination of absorptions of antisera plus amino acid sequence data we hope to be able to compare the structures of the individual determinants. Molecules of the IgA-g subclass are readily digested by most proteolytic-enzymes whereas IgA-f molecules are resistant to cleavage. One of our goals is to determine the physical chemical basis for this differential sensitivity to proteolytic digestion. This will be done by isolation of hinge-region peptides followed by amino acid sequencing studies and by studying the binding properties of secretory component to each of the subclasses. We also plan to suppress the phenotypic expression of IgA by antisera directed against the VH region as well as against the CH region. One of the purposes of this study is to determine how the secretory immune system is interrelated with the humoral immune system. By quantitative analysis of IgA allotypes in rabbits of various allogroups, we hope to identify a control gene which is controlling the quantitative expression of various rabbit allotypes. We also will determine the amount of somatic recombinations occurring between the VH and CH genes in an effort to map the heavy chain chromosomal region.
